WO2002041993A1 - Porte-echantillon, son couvercle et procede de preparation d'analyse - Google Patents

Porte-echantillon, son couvercle et procede de preparation d'analyse Download PDF

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Publication number
WO2002041993A1
WO2002041993A1 PCT/EP2001/013651 EP0113651W WO0241993A1 WO 2002041993 A1 WO2002041993 A1 WO 2002041993A1 EP 0113651 W EP0113651 W EP 0113651W WO 0241993 A1 WO0241993 A1 WO 0241993A1
Authority
WO
WIPO (PCT)
Prior art keywords
sample carrier
sample
cover
cover plate
lid
Prior art date
Application number
PCT/EP2001/013651
Other languages
German (de)
English (en)
Inventor
Nico Michaelsen
Martin Klumpp
Olaf Sollböhmer
Sabine KÖSTER
Original Assignee
Evotec Oai Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Evotec Oai Ag filed Critical Evotec Oai Ag
Priority to EP01997350A priority Critical patent/EP1341611B1/fr
Priority to DE50113066T priority patent/DE50113066D1/de
Publication of WO2002041993A1 publication Critical patent/WO2002041993A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids

Definitions

  • the invention relates to a sample carrier, in particular a titer plate with a plurality of wells, into which small samples can be introduced. Furthermore, the invention relates to a lid for sample carriers and a method for preparing for examinations.
  • the smallest samples are in particular liquids or other samples with a volume of 0.01-50 ⁇ l, in particular 0.2 - 5 ⁇ l. Likewise, the samples can be cell cultivation in this order of magnitude, preferably on a 1-5 ⁇ l scale.
  • the sample carriers can be chips.
  • Chips usually have one or more channels as recesses, which can be, for example, capillary channels and possibly one or more liquid reservoirs.
  • it can be microfluidic chips with preferably two reservoirs, which are connected via a channel. are connected. A fluid exchange takes place between the two reservoirs, which can be regulated by means of suitable valves, membranes, osmotic barriers and / or ion barriers.
  • suitable valves membranes, osmotic barriers and / or ion barriers.
  • sample components can be separated from one another with such chips.
  • Known chips are made of silicon, glass, plastic or ceramic.
  • sample carriers can also be, for example, planar plates with a hydrophobic grid. Such plates are partially coated with a hydrophobic substance, so that droplets of sample liquid form in these areas, which can then be examined. Sample carriers can also be so-called SBS microtiter plate formats and the so-called Terasaki format.
  • the wells of titer plates can be produced, for example, by etching / milling processes or by using injection molding processes and by laser processing.
  • a lid for example, by which the wells in a titer plate are sealed, sterility can be ensured and any evaporation from the wells of the titer plate can be prevented, but the desired cultivation conditions cannot be set. For example, a CO 2 content between 5 - 7% is required for optimal cell cultivation (pH regulation of the cell culture medium), which cannot be adjusted by the conventional arrangements.
  • the object of the invention is to provide a sample carrier, in particular a titer plate, a lid for a sample carrier and a method for preparing for examinations, in particular of chemical and / or biological small samples, in which or in particular evaporation of samples is essentially avoided and at the same time, optimal cultivation conditions, ie adequate sterility and precise control of the gas exchange, in particular an exact adjustment of the CO 2 content for cells in sample carriers for very small samples, can be achieved.
  • the sample holder has a receiving part for taking small samples. If the sample holder is a titer plate, the smallest samples are placed in the wells of the titer plate. Is the sample carrier around a chip, the smallest samples are introduced into channels or recesses in the chip. Accordingly, the samples are applied to the sample in a sample carrier designed as a planar plate with a hydrophobic grid, so that drops of sample material form.
  • the wells of a titer plate or the wells of a chip preferably have a volume of 0.01 to 50 ⁇ l. In particular, the volume is 0.2 to 5 ⁇ l.
  • the sample carrier has a lid, through which the receiving part is closed such that a cavity is formed between a sample surface and the lid. The lid bottom side is thus at a distance from the sample surface and generally also from the top of the receiving part.
  • the cover is designed in such a way that a saturated atmosphere in the cavity is essentially retained in the event of changing ambient conditions.
  • the lid thus has a certain vapor permeability and / or moisture absorption and / or release ability.
  • the cover is preferably designed such that it is suitable for receiving and dispensing liquid.
  • the saturated atmosphere in the cavity remains constant with changing environmental conditions such that a deviation of less than 5% from a saturation level takes place. In particular, this deviation is less than 2
  • the lid of the sample holder according to the invention preferably has a porous cover plate. This preferably consists of ceramic or glass and serves as a liquid reservoir.
  • the vapor phase that arises from the liquid, which is preferably stored in the porous cover plate, creates a saturated atmosphere in the cavity between the sample carrier and the lid, thereby preventing the evaporation of sample liquid.
  • gas exchange through the porous lid is possible, so that the optimal C0 2 concentration in the cavity can be set, for example, for cell cultivation.
  • the gas exchange takes place, for example, via pores which are not closed by wetting liquid, so that the gas can pass through the pores to the outside.
  • an indirect gas exchange also takes place in that the gas, in particular C0 2 , is dissolved in the liquid and, if appropriate, outgassed from the liquid into the cavity.
  • the cover is designed such that liquid in the form of vapor can escape from the pores of the cover material.
  • the sample carrier according to the invention is introduced into an incubator and exposed to elevated temperatures, steam escapes from the liquid-saturated pores within the lid and creates an atmosphere which is saturated with the temperature in the cavity between the sample carrier and lid.
  • a gas exchange between the environment and the cavity between the sample holder and the lid is possible due to the non-liquid-filled pores, so that, for example, the optimal C0 2 concentration in the cavity can be set very well.
  • the porous lid material Due to the porous lid material, it is also possible to avoid condensation on the inside of the lid, as liquid is absorbed into the pores sufficiently quickly and dripping down into individual wells is prevented. In this way, falsification of the examinations by dripping liquid is excluded. Furthermore, the sterility required is maintained over a long incubation period by means of such a lid. This is achieved with a lid with small pore diameters (preferably 0.2-0.5 ⁇ m), which prevents germs from penetrating from the outside. Surprisingly, there is sufficient sterility even with larger pore diameters.
  • the lid is also designed so that no liquid can penetrate from the outside.
  • the lid preferably has a shape that can be used very well in automated examination systems.
  • a porous cover plate has the particular advantage that the atmosphere in the cavity between the sample holder and the lid can be adjusted by the choice of the liquid with which the porous plate is wetted.
  • the goal is z. B. that the vapor pressure change resulting from a temperature increase in the cavity between the sample carrier and the lid is essentially achieved by evaporation of the liquid contained in the cover plate, so as to prevent the evaporation of the samples.
  • This is achieved, inter alia, by the substantially larger active surface of the porous cover plate compared to the surface of the sample carrier, so that evaporation takes place very quickly on the surface of the porous plate and the vapor pressure in the cavity is thus built up in a short time.
  • a porous film is provided instead of or in addition to the porous cover plate.
  • the porosity of the film also ensures that the saturated atmosphere in the cavity between the receiving part and the cover is essentially retained in the event of changing ambient conditions.
  • the lid has a porous film instead of the porous cover plate, it is possible to use suitable pipettes o. the like to pierce through the film in order to be able to take samples from the sample carrier or from the wells of the titer plates or to be able to feed them.
  • a film that automatically closes again can be used as the film. This is possible due to the small size of the holes created.
  • foils can also be used in which the hole is retained, since with a small number of holes the dimensions of the holes are so small that there is no appreciable impairment of the atmosphere in the cavity between the foil and the receiving part.
  • a porous film in addition to a cover plate.
  • the foil is preferred arranged between the cover plate and the receiving part. This makes it possible to ensure or adapt sterility within the sample holder by a suitable choice of the pore size of the film.
  • the pore size of the cover plate can then be selected independently of the sterility requirements.
  • a cover plate can then, for example, a textile material, a sponge or another substance suitable for liquid storage z. B. in the form of porous flakes or beads.
  • the gas permeability of the lid can be controlled by the film used.
  • the pore diameter of the porous cover plate and / or the film are preferably less than 0.5 ⁇ m, in particular less than 0.2 ⁇ m. This can ensure sterility within the sample holder. Surprisingly, adequate sterility is achieved even with larger pore diameters.
  • the invention further relates to a lid for a sample holder, in particular a titer plate.
  • the lid according to the invention preferably has a porous cover plate which can be wetted with a liquid for regulating the vapor pressure.
  • the lid can be developed in accordance with the preferred embodiments of the sample carrier described above.
  • the cover can be used to hold electrodes which, for example, extend into individual wells and cause sample components to migrate in an electrical field.
  • the cover preferably has sensors. With the help of the sensors, for example, the moisture content in the cavity between the cover and the receiving part can be determined. Appropriate control connected to the sensors can, for example, automatically rewet the lid if the moisture content is too low. It is also possible to arrange the sensors in such a way that the moisture content of the cover plate itself can be determined. It is also advantageous to provide sensors for determining substance proportions in the cavity. With such sensors, for example, the CO 2 content in the cavity can be determined.
  • the cover preferably has grip prisms, so that the cover can be handled automatically by a gripping arm.
  • the grip prisms and the dimensions of the sample carrier preferably correspond to the dimensions and the position of the grip prisms in the sample holder which is handled together with the lid. It is thus possible to handle both the lid and the receiving part of the sample holder with the same gripper arm.
  • the channels provided in the chip are preferably micro or nano channels, the width and height of which are in the range from 1 ⁇ m to 1 mm. Electrodes can also be arranged within the channels, for example.
  • the sample carrier according to the invention is in particular for storing reagents, for storing samples, such as cells or other test substances, for separating liquid, for example by means of CE or CEC, for manipulating the Samples, for example by electroporation, electropermeation or hybridization and the like. be used.
  • sample carrier or the like a transparent glass plate. contains, so that the samples can be used by means of fluorescence correlation spectroscopy, in particular using convocal optics.
  • optical tweezers can also be used to hold particles in such sample carriers.
  • the invention further comprises a method for the preparation of examinations of chemical and / or biological small samples.
  • small samples with a volume of preferably 0.2-5 ⁇ l are introduced into wells of the sample carrier, in particular into wells of the titer plate.
  • the sample holder is then closed with a lid, which preferably has a porous cover plate.
  • the porous cover plate can advantageously be developed as described above.
  • the porous cover plate is wetted with a liquid. This achieves vapor pressure regulation in the cavity formed between the top of the sample and the lid.
  • the method according to the invention has the advantages described above with regard to the use of a lid with a porous cover plate.
  • the lid is preferably sterilized before the sample holder is closed. This prevents germs from getting into the samples when the sample carrier is closed.
  • a PBS buffer with at least 0.7% sodium chloride is preferably used as the liquid.
  • a buffer solution is preferably used which has essentially the same vapor pressure. points out how the samples contained in the wells. It is also advantageous to use a liquid with a pH of 7-8, in particular 7.5.
  • Fig. 1 is a schematic plan view of a sample holder according to the invention with a lid and
  • the cover 10 visible in FIG. 1 has a porous cover plate 12 which is carried by a holding part 14.
  • the embodiment shown is a frame-shaped holding part 14 which completely surrounds the cover plate 12.
  • the cover plate 12 can be glued into the holding part 14.
  • supports 16 (FIG. 2) are introduced into the holding part 14.
  • the supports 16 are L-shaped in cross-section and project inwards from the frame-shaped holding part 14, so that the cover plate 12 can be inserted into the cover 10 from above and lies on the supports 16.
  • the supports 16 are preferably also frame-shaped, so that they run completely along the inner edge 18 of the holding part 14. However, individual pads 16 can also be arranged distributed on the inner circumference 18 of the frame.
  • a sample carrier 20 (FIG. 2) has a frame-shaped holding part 22 with a rectangular opening.
  • a receiving part 24 with depressions 26 is arranged in this. The samples are accommodated in the depressions 26.
  • the receiving part 24 is made of plastic, for example, and has 26 through openings as recesses. These are closed on the underside, preferably with a glass plate 28.
  • the cover 10 has a sealing lip 30 on the cover plate 12 or the holding part 14 pointing in the direction of the receiving part 24.
  • the sealing lip 30 is connected to the holding part 14 via the support 16.
  • the sealing lip 30 is thus rectangular corresponding to the opening in the frame-shaped holding part 22.
  • a cavity 38 is formed between an underside 34 of the cover plate 12 and an upper side 36 of the receiving part 24.
  • a vapor pressure is formed in the cavity 38 due to the very low evaporation of liquid from the depressions 26 and due to the main evaporation of the liquid provided in the porous cover plate 12.
  • the lower part of the cavity 38 forms a recess in the sample carrier 20.
  • the sealing lip 30 engages in this recess in order to fix the position.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Analysing Materials By The Use Of Radiation (AREA)

Abstract

Un porte-échantillon, notamment une plaque-titre, présente des creux (26) dans un élément récepteur (24). Ces creux contiennent des micro-échantillons d'un volume, de préférence, de 0,2 à 5 νl. Les creux (26) sont fermés par un couvercle (10). Pour réduire l'évaporation des échantillons dans une cavité (38), le couvercle (10) présente, de préférence, une plaque de recouvrement poreuse (12), cette plaque pouvant être mouillée par un liquide.
PCT/EP2001/013651 2000-11-23 2001-11-23 Porte-echantillon, son couvercle et procede de preparation d'analyse WO2002041993A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP01997350A EP1341611B1 (fr) 2000-11-23 2001-11-23 Porte-echantillon, son couvercle et procede de preparation d'analyse
DE50113066T DE50113066D1 (de) 2000-11-23 2001-11-23 Probenträger, deckel für probenträger und verfahren zur untersuchungsvorbereitung

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10058108A DE10058108A1 (de) 2000-11-23 2000-11-23 Probenträger, Deckel für Probenträger und Verfahren zur Untersuchungsvorbereitung
DE10058108.0 2000-11-23

Publications (1)

Publication Number Publication Date
WO2002041993A1 true WO2002041993A1 (fr) 2002-05-30

Family

ID=7664348

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/013651 WO2002041993A1 (fr) 2000-11-23 2001-11-23 Porte-echantillon, son couvercle et procede de preparation d'analyse

Country Status (4)

Country Link
EP (1) EP1341611B1 (fr)
AT (1) ATE374077T1 (fr)
DE (2) DE10058108A1 (fr)
WO (1) WO2002041993A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10352716A1 (de) * 2003-11-05 2005-06-16 Einsle, Xaver Plattform
DE102004041941B4 (de) * 2004-08-30 2007-01-11 P.A.L.M. Microlaser Technologies Ag Verfahren zur Gewinnung von biologischen Objekten mit einer Aufnahmeeinheit
DE102006048264B4 (de) * 2006-10-12 2011-03-24 Bundesrepublik Deutschland, vertreten durch das Bundesministerium der Verteidigung, vertreten durch das Bundesamt für Wehrtechnik und Beschaffung Verfahren zum Nachweis spezifischer Nukleinsäuresequenzen
US8222048B2 (en) 2007-11-05 2012-07-17 Abbott Laboratories Automated analyzer for clinical laboratory
DE102011004449B4 (de) * 2011-02-21 2019-01-24 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Biopsieplättchen, Einbettkassette und Diagnosevorrichtung

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0388159A2 (fr) * 1989-03-15 1990-09-19 Seiko Instruments Inc. Dispositif pour le scellement d'un liquide dans des cavités
WO1995027196A1 (fr) * 1994-04-04 1995-10-12 Sanadi Ashok R Procede et appareil destine a empecher la contamination croisee de plaques de test a cupules multiples
US5516490A (en) * 1993-04-19 1996-05-14 Sanadi Biotech Group, Inc. Apparatus for preventing cross-contamination of multi-well test plates
WO1997019754A1 (fr) * 1995-11-27 1997-06-05 Boehringer Mannheim Gmbh Article servant a recueillir et transporter un echantillon a analyser, et procede de determination d'un analyte
US5789251A (en) * 1994-06-16 1998-08-04 Astle; Thomas W. Multi-well bioassay tray with evaporation protection and method of use
WO2000003805A1 (fr) * 1998-07-15 2000-01-27 Combichem, Inc. Systeme de reaction chimique par microtitrage

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE1010984A3 (nl) * 1995-02-17 1999-03-02 Praet Peter Van Incubator voor microtiter plaat.
US5587321A (en) * 1995-07-31 1996-12-24 University Of Kansas Moated tissue culture plate
DE29619444U1 (de) * 1996-11-08 1997-01-09 Canberra-Packard GmbH, 63303 Dreieich Pipettiervorrichtung
US5908776A (en) * 1998-04-06 1999-06-01 Pharmacopeia, Inc. Cell culture chamber for multiple well plates

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0388159A2 (fr) * 1989-03-15 1990-09-19 Seiko Instruments Inc. Dispositif pour le scellement d'un liquide dans des cavités
US5516490A (en) * 1993-04-19 1996-05-14 Sanadi Biotech Group, Inc. Apparatus for preventing cross-contamination of multi-well test plates
WO1995027196A1 (fr) * 1994-04-04 1995-10-12 Sanadi Ashok R Procede et appareil destine a empecher la contamination croisee de plaques de test a cupules multiples
US5789251A (en) * 1994-06-16 1998-08-04 Astle; Thomas W. Multi-well bioassay tray with evaporation protection and method of use
WO1997019754A1 (fr) * 1995-11-27 1997-06-05 Boehringer Mannheim Gmbh Article servant a recueillir et transporter un echantillon a analyser, et procede de determination d'un analyte
WO2000003805A1 (fr) * 1998-07-15 2000-01-27 Combichem, Inc. Systeme de reaction chimique par microtitrage

Also Published As

Publication number Publication date
DE10058108A1 (de) 2002-06-06
EP1341611B1 (fr) 2007-09-26
DE50113066D1 (de) 2007-11-08
ATE374077T1 (de) 2007-10-15
EP1341611A1 (fr) 2003-09-10

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